Journal of Clinical Oncology, Vol 16, 610-615, Copyright © 1998 by American Society of Clinical Oncology
Plasma concentrations and pharmacokinetics of dimethylsulfoxide and its metabolites in patients undergoing peripheral-blood stem-cell transplants
MJ Egorin, DM Rosen, R Sridhara, L Sensenbrenner and M Cottler-Fox
Division of Developmental Therapeutics, University of Maryland Cancer Center, Baltimore 21201, USA. megorin@umaryland.edu
PURPOSE: Dimethylsulfoxide (DMSO) is used to cryopreserve hematopoietic
stem cells and is obligatorily infused into patients who receive stem- cell
transplants. This study characterized the plasma concentrations and
pharmacokinetics of DMSO and its metabolites in patients who underwent
peripheral-blood stem-cell transplants. MATERIALS AND METHODS: Plasma
concentrations of DMSO, dimethylsulfone (DMSO2), and dimethylsulfide
(DMSH2) were assessed in 10 patients who underwent autologous transplants
with stem cells, cryopreserved in 10% DMSO (vol/vol). Blood was sampled at
multiple times after the stem-cell infusion. Urine was pooled during the 24
hours postinfusion. DMSO, DMSO2, and DMSH2 were assayed simultaneously by
gas chromatography. A one-compartment model with saturable elimination
proved most suitable for fitting plasma DMSO concentration-versus-time
data. RESULTS: Stem- cell volumes infused ranged between 180 and 585 mL
(254 to 824 mmol DMSO). Infusions lasted between 20 and 120 minutes. Peak
plasma DMSO concentrations were 19.1 +/- 6.3 mmol/L (mean +/- SD).
Pharmacokinetic parameters for volume of the central compartment (Vc),
maximum velocity (Vmax), and Michaels-Menten constant (Km) were 37.3 +/- 17
L, 0.99 +/- 0.57 mmol/L/h, and 5.2 +/- 5.0 mmol/L, respectively. Plasma
DMSO2 concentrations increased during the first 24 hours, plateaued at 4.4
+/- 1.2 mmol/L, and remained there until 48 hours (the last sample). DMSH2
concentrations were at steady-state by 5 minutes and remained between 3 and
5 mmol/L for 48 hours. Urinary excretion of DMSO and DMSO2 accounted for
44% +/- 4% and 4% +/- 1%, respectively, of the administered DMSO dose.
Renal clearance of DMSO was 14.1 +/- 3.4 mL/min. CONCLUSION: These data (1)
document plasma concentrations of DMSO and metabolites in patients
following peripheral-blood stem-cell transplants; (2) allow consideration
of potential effects of these concentrations on stem-cell engraftment and
drug-drug interactions; and (3) can facilitate a concentration-guided phase
I trial of DMSO.
